The major area of study of this laboratory is the role of the epidermis as an immunological tissue. We have found that epidermal Langerhans cells are derived from precursors in the bone marrow and play an essential role in many of the immunological reactions affecting the skin. We have also identified an epidermal Interleukin 1-like cytokine which may serve as a second signal in the generation of T cell responses as well as a promflammatory agent affecting other cells - especially neutrophils. During the past year we have demonstrated that when epidermal Langerhans cells are cultured for 2-3 days they become very potent antigen presenting cells compared to freshly prepared Langerhans cells. We have therefore utilized cultured Langerhans cells for the generation of primary immune responses in resting unsensitized T cells. We have demonstrated that when cultured cells are modified with hapten, they can generate primary immune responses. The sensitized T cells thus generated respond preferentially to the same hapten in vitro. We have also concentrated our efforts on the characterization of murine dendritic thy 1 positive epidermal cells. We have utilized highly enriched populations of freshly prepared cells and identified their T cell nature by demonstrating that they express alpha and beta chain message for the T cell antigen receptor. Furthermore we have cultured these cells from nude mice and have found that they express the entire T cell antigen receptor on their membrane. These cells may therefore represent an extra thymic source of T cells in nude as well as normal mice.